Developmental-ecological theory posits that the initiation of substance use (SU) in childhood and adolescence is a function of reciprocal and interacting influences between individuals and their socio- environmental context. Yet, very little research has integrated risk and protective factors from multiple levels. Theoretically grounded research that delineates unique and interactive individual and contextual influences on early emerging SU is needed to guide the development of preventive interventions. We propose to test mediational and moderational relations among cognitive, peer, parental, community, and psychobiological/motivational factors as pathways to adolescent SU. Research in neuroscience suggests that changes in appetitive motivation during adolescence increases vulnerability to risky contexts. The proposed research will examine how shifts in appetitive motivation converge with community, parental, and peer contexts to influence both implicit and explicit beliefs supportive of SU and SU. A sample of 400 10-12 year old children assessed across 3-waves will allow for the examination of how changes in these constructs presage SU. Child motivational profiles based on approach, inhibition, and self-regulation will be assessed using laboratory tasks, physiological indicators, and parent reports. Multiple methods will be used to assess beliefs about SU, and peer, parental, and community context. A combination of latent profile, transition, multilevel, and growth analysis, will be used to examine: 1) trajectories of SU beliefs;2) the direct, indirect, and reciprocal effects of context on SU beliefs and SU;and 3) the moderating effect of motivational profiles on the relation between context and beliefs and SU. This study examines developmental changes in beliefs related to adolescent SU, and modulation of contextual influences by psychobiological motivational profiles. The proposed research has the potential to provide important direction for how the content of SU preventive interventions could be tailored for specific populations and to target relevant etiological processes for maximal effectiveness.